title: Connexin40 regulates platelet function.
abstract: The presence of multiple connexins was recently demonstrated in platelets, with notable expression of Cx37. Studies with Cx37-deficient mice and connexin inhibitors established roles for hemichannels and gap junctions in platelet function. It was uncertain, however, whether Cx37 functions alone or in collaboration with other family members through heteromeric interactions in regulation of platelet function. Here we report the presence and functions of an additional platelet connexin, Cx40. Inhibition of Cx40 in human platelets or its deletion in mice reduces platelet aggregation, fibrinogen binding, granule secretion and clot retraction. The effects of the Cx37 inhibitor (37,43)Gap27 on Cx40(-/-) mouse platelets and of the Cx40 inhibitor (40)Gap27 on Cx37(-/-) mouse platelets revealed that each connexin is able to function independently. Inhibition or deletion of Cx40 reduces haemostatic responses in mice, indicating the physiological importance of this protein in platelets. We conclude that multiple connexins are involved in regulating platelet function, thereby contributing to haemostasis and thrombosis.
authors.affiliation: Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Harborne Building, Whiteknights, RG6 6AS Reading, UK.
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Vaiyapuri
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Moraes
authors.forename: Tanya
authors.initials: T
authors.lastname: Sage
authors.forename: Marfoua S
authors.initials: MS
authors.lastname: Ali
authors.forename: Kirsty R
authors.initials: KR
authors.lastname: Lewis
authors.forename: Martyn P
authors.initials: MP
authors.lastname: Mahaut-Smith
authors.forename: Ernesto
authors.initials: E
authors.lastname: Oviedo-Orta
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Simon
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gibbins
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D015550:Cell Degranulation / Q000187:drug effects; D017630:Connexins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D015398:Signal Transduction; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D017630:Connexins; D010455:Peptides; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein